chr16-4508063-G-A

Position:

• chr16-4508063-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_002134.4(HMOX2):​c.555G>A​(p.Gln185=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 1,614,158 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0031 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (15 hom.)
• Consequence: HMOX2 NM_002134.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200

Genes affected

HMOX2 (HGNC:5014): (heme oxygenase 2) Heme oxygenase, an essential enzyme in heme catabolism, cleaves heme to form biliverdin, which is subsequently converted to bilirubin by biliverdin reductase, and carbon monoxide, a putative neurotransmitter. Heme oxygenase activity is induced by its substrate heme and by various nonheme substances. Heme oxygenase occurs as 2 isozymes, an inducible heme oxygenase-1 and a constitutive heme oxygenase-2. HMOX1 and HMOX2 belong to the heme oxygenase family. Several alternatively spliced transcript variants encoding three different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=0.02 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMOX2	NM_002134.4	c.555G>A	p.Gln185=	synonymous_variant	4/6	ENST00000570646.6	NP_002125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMOX2	ENST00000570646.6	c.555G>A	p.Gln185=	synonymous_variant	4/6	1	NM_002134.4	ENSP00000459214	P1

Frequencies

GnomAD3 genomes AF: 0.00308 AC: 469 AN: 152168 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00538

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00265 AC: 666 AN: 251366 Hom.: 3 AF XY: 0.00266 AC XY: 361 AN XY: 135894

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00407

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00157

Gnomad NFE exome AF: 0.00451

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00433 AC: 6333 AN: 1461872 Hom.: 15 Cov.: 32 AF XY: 0.00431 AC XY: 3133 AN XY: 727240

Gnomad4 AFR exome AF: 0.000657

Gnomad4 AMR exome AF: 0.00141

Gnomad4 ASJ exome AF: 0.00474

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000243

Gnomad4 FIN exome AF: 0.00234

Gnomad4 NFE exome AF: 0.00516

Gnomad4 OTH exome AF: 0.00391

GnomAD4 genome AF: 0.00308 AC: 469 AN: 152286 Hom.: 3 Cov.: 32 AF XY: 0.00305 AC XY: 227 AN XY: 74470

Gnomad4 AFR AF: 0.000698

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.00538

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00385 Hom.: 1

Bravo AF: 0.00274

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00458

EpiControl AF: 0.00439

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.9
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2404579; hg19: chr16-4558064;